Whole Exome Sequencing Gene package Epilepsy, version 1, 8‐4‐2015

Technical information After DNA was enriched using Agilent Sureselect Clinical Research Exome (CRE) Capture, samples were run on the Illumina Hiseq platform. The aim is to obtain 50 million total reads per exome with a mapped fraction >0.98. The average coverage of the exome is ~50x. Data are demultiplexed by Illumina software bcl2fastq. Reads are mapped to the genome using BWA (reference: http://bio‐bwa.sourceforge.net/). Variant detection is performed by Genome Analysis Toolkit (reference: http://www.broadinstitute.org/gatk/). Analysis is performed in Cartagenia using The Variant Calling File (VCF) followed by filtering. It is not excluded that pathogenic mutations are being missed using this technology. At this moment, there is not enough information about the sensitivity of this technique with respect to the detection of deletions and duplications of more than 5 nucleotides and of somatic mosaic mutations (all types of sequence changes).

HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered gene symbol gene ID >10x >20x ABAT GABA‐transaminase deficiency, 613163 137150 77 100 99 ABCC8 Hyperinsulinemic hypoglycemia, familial, 1, 256450 600509 83 100 100 Hypoglycemia of infancy, leucine‐sensitive, 240800 Diabetes mellitus, transient neonatal 2, 610374 Diabetes mellitus, noninsulin‐dependent, 125853 Diabetes mellitus, permanent neonatal, 606176 ACY1 Aminoacylase 1 deficiency, 609924 104620 84 100 100 ADSL Adenylosuccinase deficiency, 103050 608222 86 100 100 ALDH7A1 Epilepsy, pyridoxine‐dependent, 266100 107323 76 100 99 ALG13 Epileptic encephalopathy, early infantile, 36, 300884 300776 30 88 60 AMACR Alpha‐methylacyl‐CoA racemase deficiency, 614307 604489 81 100 98 Bile acid synthesis defect, congenital, 4, 214950 AMT Glycine encephalopathy, 605899 238310 91 100 100 ARHGEF9 Epileptic encephalopathy, early infantile, 8, 300607 300429 47 100 87 ARX Epileptic encephalopathy, early infantile, 1, 308350 300382 24 84 61 Lissencephaly, X‐linked 2, 300215 Mental retardation, X‐linked 29 and others, 300419 Proud syndrome, 300004 Partington syndrome, 309510 Hydranencephaly with abnormal genitalia, 300215

Whole exome sequencing Gene package Epilepsy version 1, 8‐4‐2015 HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered gene symbol gene ID >10x >20x ASAH1 Farber lipogranulomatosis, 228000 613468 77 100 99 Spinal muscular atrophy with progressive myoclonic epilepsy, 159950 ATP1A2 Migraine, familial hemiplegic, 2, 602481 182340 109 100 100 Alternating hemiplegia of childhood, 104290 Migraine, familial basilar, 602481 ATP6AP2 ?Mental retardation, X‐linked, syndromic, Hedera type, 300423 300556 39 100 90 ?Parkinsonism with spasticity, X‐linked, 300911 ATP7A Menkes disease, 309400 300011 53 99 94 Occipital horn syndrome, 304150 Spinal muscular atrophy, distal, X‐linked 3, 300489 ATRX Alpha‐thalassemia/mental retardation syndrome, 301040 300032 38 98 83 Alpha‐thalassemia myelodysplasia syndrome, somatic, 300448 Mental retardation‐hypotonic facies syndrome, X‐linked, 309580 BOLA3 Multiple mitochondrial dysfunctions syndrome 2, 614299 613183 38 83 63 BTD Biotinidase deficiency, 253260 609019 105 100 100 CACNA1A Migraine, familial hemiplegic, 1, 141500 601011 74 100 95 Episodic ataxia, type 2, 108500 Spinocerebellar ataxia 6, 183086 Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, 141500 CASK Mental retardation and microcephaly with pontine and cerebellar hypoplasia, 300749 300172 39 98 87 FG syndrome 4, 300422 Mental retardation, with or without nystagmus, 300422 CDKL5 Epileptic encephalopathy, early infantile, 2, 300672 300203 47 98 94 CHD2 Epileptic encephalopathy, childhood‐onset, 615369 602119 75 100 98 CHRNA2 Epilepsy, nocturnal frontal lobe, type 4, 610353 118502 119 100 100 CHRNA4 Epilepsy, nocturnal frontal lobe, 1, 600513 118504 91 97 94 {Nicotine addiction, susceptibility to}, 188890 CHRNB2 Epilepsy, nocturnal frontal lobe, 3, 605375 118507 102 100 97 CLDN16 Hypomagnesemia 3, renal, 248250 603959 92 100 100 CLDN19 Hypomagnesemia 5, renal, with ocular involvement, 248190 610036 79 100 97 CLN3 Ceroid lipofuscinosis, neuronal, 3, 204200 607042 68 100 100 CLN5 Ceroid lipofuscinosis, neuronal, 5, 256731 608102 73 100 94 CLN6 Ceroid lipofuscinosis, neuronal, 6, 601780 606725 72 100 91 Ceroid lipofuscinosis, neuronal, Kufs type, adult onset, 204300 CLN8 Ceroid lipofuscinosis, neuronal, 8, 600143 607837 100 100 100 Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant, 610003 CNNM2 Hypomagnesemia 6, renal, 613882 607803 113 100 100 Hypomagnesemia, seizures, and mental retardation, 616418 CNTN2 ?Epilepsy, myoclonic, familial adult, 5, 615400 190197 60 100 95

Whole exome sequencing Gene package Epilepsy version 1, 8‐4‐2015 HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered gene symbol gene ID >10x >20x CNTNAP2 Cortical dysplasia‐focal epilepsy syndrome, 610042 604569 85 100 100 {Autism susceptibility 15}, 612100 Pitt‐Hopkins like syndrome 1, 610042 COQ2 Coenzyme Q10 deficiency, primary, 1, 607426 609825 60 100 94 {Multiple system atrophy, susceptibility to}, 146500 CPA6 Epilepsy, familial temporal lobe, 5, 614417 609562 104 100 100 Febrile seizures, familial, 11, 614418 CPS1 Carbamoylphosphate synthetase I deficiency, 237300 608307 78 100 99 {Pulmonary hypertension, neonatal, susceptibility to}, 615371 {Venoocclusive disease after bone marrow transplantation} CPT2 Myopathy due to CPT II deficiency, 255110 600650 120 99 96 CPT deficiency, hepatic, type II, 600649 CPT II deficiency, lethal neonatal, 608836 {Encephalopathy, acute, infection‐induced, 4, susceptibility to}, 614212 CSTB Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), 254800 601145 124 100 97 CTSD Ceroid lipofuscinosis, neuronal, 10, 610127 116840 83 100 96 CTSF Ceroid lipofuscinosis, neuronal, 13, Kufs type, 615362 603539 43 82 70 CUL4B Mental retardation, X‐linked, syndromic 15 (Cabezas type), 300354 300304 39 100 92 D2HGDH D‐2‐hydroxyglutaric aciduria, 600721 609186 91 100 100 DCX Lissencephaly, X‐linked, 300067 300121 47 98 85 Subcortical laminal heteropia, X‐linked, 300067 DEPDC5 Epilepsy, familial focal, with variable foci, 604364 614191 53 99 90 DLAT Pyruvate dehydrogenase E2 deficiency, 245348 608770 62 100 95 DNAJC5 Ceroid lipofuscinosis, neuronal, 4, Parry type, 162350 611203 111 100 100 DPYD Dihydropyrimidine dehydrogenase deficiency, 274270 612779 79 98 95 5‐fluorouracil toxicity, 274270 DYNC1H1 Charcot‐Marie‐Tooth disease, axonal, type 20, 614228 600112 86 100 99 Mental retardation, autosomal dominant 13, 614563 Spinal muscular atrophy, lower extremity‐predominant 1, AD, 158600 DYRK1A Mental retardation, autosomal dominant 7, 614104 600855 99 100 100 EEF1A2 Mental retardation, autosomal dominant 38, 616393 602959 78 100 96 Epileptic encephalopathy, early infantile, 33, 616409 EGF Hypomagnesemia 4, renal, 611718 131530 80 100 100 EHMT1 Kleefstra syndrome, 610253 607001 97 99 99 EPM2A Epilepsy, progressive myoclonic 2A (Lafora), 254780 607566 66 87 83 FARS2 Combined oxidative phosphorylation deficiency 14, 614946 611592 101 100 100 FGD1 Aarskog‐Scott syndrome, 305400 300546 43 99 87 Mental retardation, X‐linked syndromic 16, 305400

Whole exome sequencing Gene package Epilepsy version 1, 8‐4‐2015 HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered gene symbol gene ID >10x >20x FLNA Heterotopia, periventricular, 300049 300017 55 100 99 Otopalatodigital syndrome, type I, 311300 Otopalatodigital syndrome, type II, 304120 Intestinal pseudoobstruction, neuronal, 300048 Melnick‐Needles syndrome, 309350 Frontometaphyseal dysplasia, 305620 Heterotopia, periventricular, ED variant, 300537 FG syndrome 2, 300321 Cardiac valvular dysplasia, X‐linked, 314400 Terminal osseous dysplasia, 300244 Congenital short bowel syndrome, 300048 FOLR1 Neurodegeneration due to cerebral folate transport deficiency, 613068 136430 94 100 100 FOXG1 Rett syndrome, congenital variant, 613454 164874 80 83 77 FOXRED1 Leigh syndrome due to mitochondrial complex I deficiency, 256000 613622 74 100 100 Mitochondrial complex I deficiency, 252010 FXYD2 Hypomagnesemia 2, renal, 154020 601814 49 100 91 GABRA1 {Epilepsy, juvenile myoclonic, susceptibility to, 5}, 611136 137160 95 100 100 {Epilepsy, childhood absence, susceptibility to, 4}, 611136 Epileptic encephalopathy, early infantile, 19, 615744 GABRG2 Epilepsy, generalized, with febrile seizures plus, type 3, 611277 137164 107 99 92 {Epilepsy, childhood absence, susceptibility to, 2}, 607681 Febrile seizures, familial, 8, 611277 GAMT Cerebral creatine deficiency syndrome 2, 612736 601240 59 99 89 GCK MODY, type II, 125851 138079 84 100 100 Diabetes mellitus, noninsulin‐dependent, late onset, 125853 Hyperinsulinemic hypoglycemia, familial, 3, 602485 Diabetes mellitus, permanent neonatal, 606176 GCSH Glycine encephalopathy, 605899 238330 14 61 18 GLDC Glycine encephalopathy, 605899 238300 36 81 62 GLRA1 Hyperekplexia, hereditary 1, autosomal dominant or recessive, 149400 138491 73 100 99 GLRB Hyperekplexia 2, autosomal recessive, 614619 138492 65 100 99 GLUD1 Hyperinsulinism‐hyperammonemia syndrome, 606762 138130 25 80 50 GNAO1 Epileptic encephalopathy, early infantile, 17, 615473 139311 66 100 99 GPC3 Simpson‐Golabi‐Behmel syndrome, type 1, 312870 300037 38 98 92 Wilms tumor, somatic, 194070 GPHN Molybdenum cofactor deficiency C, 615501 603930 80 100 98 GRIA3 Mental retardation, X‐linked 94, 300699 305915 54 100 98 GRIN1 Mental retardation, autosomal dominant 8, 614254 138249 96 100 99 GRIN2A Epilepsy, focal, with speech disorder and with or without mental retardation, 245570 138253 80 100 100

Whole exome sequencing Gene package Epilepsy version 1, 8‐4‐2015 HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered gene symbol gene ID >10x >20x GRIN2B Mental retardation, autosomal dominant 6, 613970 138252 95 100 100 Epileptic encephalopathy, early infantile, 27, 616139 GRN Frontotemporal lobar degeneration with ubiquitin‐positive inclusions, 607485 138945 95 100 100 Aphasia, primary progressive, 607485 Ceroid lipofuscinosis, neuronal, 11, 614706 HADH 3‐hydroxyacyl‐CoA dehydrogenase deficiency, 231530 601609 85 100 100 Hyperinsulinemic hypoglycemia, familial, 4, 609975 HDAC4 No OMIM phenotype 605314 73 100 100 HLCS Holocarboxylase synthetase deficiency, 253270 609018 88 100 100 HNRNPU No OMIM phenotype 602869 73 100 97 HSD17B10 17‐beta‐hydroxysteroid dehydrogenase X deficiency, 300438 300256 63 100 100 ?Mental retardation, X‐linked syndromic 10, 300220 HSD17B4 D‐bifunctional protein deficiency, 261515 601860 63 99 96 Perrault syndrome 1, 233400 IDH2 D‐2‐hydroxyglutaric aciduria 2, 613657 147650 79 100 98 IER3IP1 Microcephaly, epilepsy, and diabetes syndrome, 614231 609382 60 78 78 IQSEC2 Mental retardation, X‐linked 1, 309530 300522 38 94 84 KANSL1 Koolen‐De Vries syndrome, 610443 612452 65 97 86 KCNA1 Episodic ataxia/myokymia syndrome, 160120 176260 81 100 100 KCNJ10 SESAME syndrome, 612780 602208 122 100 100 Enlarged vestibular aqueduct, digenic, 600791 KCNJ11 Hyperinsulinemic hypoglycemia, familial, 2, 601820 600937 104 100 100 Diabetes, permanent neonatal, 606176 Diabetes mellitus, permanent neonatal, with neurologic features, 606176 {Diabetes mellitus, type 2, susceptibility to}, 125853 Diabetes mellitus, transient neonatal, 3, 610582 Maturity‐onset diabetes of the young, type 13, 616329 KCNMA1 Generalized epilepsy and paroxysmal dyskinesia, 609446 600150 73 100 97 KCNQ2 Seizures, benign neonatal, 1, 121200 602235 70 100 100 Myokymia, 121200 Epileptic encephalopathy, early infantile, 7, 613720 KCNQ3 Seizures, benign neonatal, type 2, 121201 602232 85 100 96 KCNT1 Epileptic encephalopathy, early infantile, 14, 614959 608167 86 100 99 Epilepsy, nocturnal frontal lobe, 5, 615005 KCTD7 Epilepsy, progressive myoclonic 3, with or without intracellular inclusions, 611726 611725 90 100 100 KDM5C Mental retardation, X‐linked, syndromic, Claes‐Jensen type, 300534 314690 52 100 96 LGI1 Epilepsy, familial temporal lobe, 1, 600512 604619 86 100 100 LIAS Pyruvate dehydrogenase lipoic acid synthetase deficiency, 614462 607031 85 100 97 MBD5 Mental retardation, autosomal dominant 1, 156200 611472 82 100 100

Whole exome sequencing Gene package Epilepsy version 1, 8‐4‐2015 HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered gene symbol gene ID >10x >20x MECP2 Rett syndrome, 312750 300005 52 99 81 Mental retardation, X‐linked, syndromic 13, 300055 Rett syndrome, preserved speech variant, 312750 Encephalopathy, neonatal severe, 300673 {Autism susceptibility, X‐linked 3}, 300496 Mental retardation, X‐linked syndromic, Lubs type, 300260 Rett syndrome, atypical, 312750 MED12 Opitz‐Kaveggia syndrome, 305450 300188 47 100 91 Lujan‐Fryns syndrome, 309520 Ohdo syndrome, X‐linked, 300895 MEF2C Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations, 613443 600662 66 100 98 Chromosome 5q14.3 deletion syndrome, 613443 MFSD8 Ceroid lipofuscinosis, neuronal, 7, 610951 611124 75 100 97 Macular dystrophy with central cone involvement, 616170 MOCS1 Molybdenum cofactor deficiency A, 252150 603707 67 93 77 MOCS2 Molybdenum cofactor deficiency B, 252160 603708 73 100 100 MTHFR Homocystinuria due to MTHFR deficiency, 236250 607093 94 100 100 {Schizophrenia, susceptibility to}, 181500 {Vascular disease, susceptibility to} {Neural tube defects, susceptibility to}, 601634 {Thromboembolism, susceptibility to}, 188050 MTOR Smith‐Kingsmore syndrome, 616638 601231 47 98 86 NDUFA1 Mitochondrial complex I deficiency, 252010 300078 85 100 90 NDUFA11 Mitochondrial complex I deficiency, 252010 612638 57 100 96 NDUFAF1 Mitochondrial complex I deficiency, 252010 606934 81 100 100 NDUFAF2 Mitochondrial complex I deficiency, 252010 609653 14 65 23 Leigh syndrome, 256000 NDUFAF3 Mitochondrial complex I deficiency, 252010 612911 83 100 100 NDUFAF4 Mitochondrial complex I deficiency, 252010 611776 71 100 100 NDUFAF5 Mitochondrial complex 1 deficiency, 252010 612360 67 100 95 NDUFB3 Mitochondrial complex I deficiency, 252010 603839 47 65 48 NDUFB9 ?Mitochondrial complex I deficiency, 252010 601445 90 100 100 NDUFS1 Mitochondrial complex I deficiency, 252010 157655 76 100 98 NDUFS2 Mitochondrial complex I deficiency, 252010 602985 89 100 100 NDUFS3 Leigh syndrome due to mitochondrial complex I deficiency, 256000 603846 126 100 100 Mitochondrial complex I deficiency, 252010 NDUFS4 Leigh syndrome, 256000 602694 81 100 100 Mitochondrial complex I deficiency, 252010 NDUFS6 Mitochondrial complex I deficiency, 252010 603848 65 100 85

Whole exome sequencing Gene package Epilepsy version 1, 8‐4‐2015 HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered gene symbol gene ID >10x >20x NDUFV1 Mitochondrial complex I deficiency, 252010 161015 92 100 100 NDUFV2 Mitochondrial complex I deficiency, 252010 600532 30 68 36 NECAP1 ?Epileptic encephalopathy, early infantile, 21, 615833 611623 45 100 93 NEDD4L No OMIM phenotype 606384 84 100 97 NHLRC1 Epilepsy, progressive myoclonic 2B (Lafora), 254780 608072 86 100 100 NRXN1 Pitt‐Hopkins‐like syndrome 2, 614325 600565 102 100 99 {Schizophrenia, susceptibility to, 17}, 614332 NUBPL Mitochondrial complex I deficiency, 252010 613621 55 100 92 OFD1 Orofaciodigital syndrome I, 311200 300170 43 99 88 Simpson‐Golabi‐Behmel syndrome, type 2, 300209 Joubert syndrome 10, 300804 ?Retinitis pigmentosa 23, 300424 OPHN1 Mental retardation, X‐linked, with cerebellar hypoplasia and distinctive facial appearance, 300486 300127 42 100 97 PAK3 Mental retardation, X‐linked 30/47, 300558 300142 41 99 86 PC Pyruvate carboxylase deficiency, 266150 608786 84 100 100 PCDH19 Epileptic encephalopathy, early infantile, 9, 300088 300460 57 100 97 PDHA1 Pyruvate dehydrogenase E1‐alpha deficiency, 312170 300502 64 99 92 PDHB Pyruvate dehydrogenase E1‐beta deficiency, 614111 179060 79 100 100 PDP1 Pyruvate dehydrogenase phosphatase deficiency, 608782 605993 83 100 100 PEX1 Peroxisome biogenesis disorder 1A (Zellweger), 214100 602136 67 100 98 Peroxisome biogenesis disorder 1B (NALD/IRD), 601539 Heimler syndrome 1, 234580 PEX10 Peroxisome biogenesis disorder 6A (Zellweger), 614870 602859 60 95 89 Peroxisome biogenesis disorder 6B, 614871 PEX12 Peroxisome biogenesis disorder 3A (Zellweger), 614859 601758 104 100 100 Peroxisome biogenesis disorder 3B, 266510 PEX13 Peroxisome biogenesis disorder 11A (Zellweger), 614883 601789 91 100 100 Peroxisome biogenesis disorder 11B, 614885 PEX14 Peroxisome biogenesis disorder 13A (Zellweger), 614887 601791 85 100 100 PEX16 Peroxisome biogenesis disorder 8A, (Zellweger), 614876 603360 85 100 95 Peroxisome biogenesis disorder 8B, 614877 PEX19 Peroxisome biogenesis disorder 12A (Zellweger), 614886 600279 75 100 100 PEX26 Peroxisome biogenesis disorder 7A (Zellweger), 614872 608666 94 100 100 Peroxisome biogenesis disorder 7B, 614873 PEX3 Peroxisome biogenesis disorder 10A (Zellweger), 614882 603164 58 100 98 PEX5 Peroxisome biogenesis disorder 2A (Zellweger), 214110 600414 93 100 100 Peroxisome biogenesis disorder 2B, 202370 Rhizomelic chondrodysplasia punctata, type 5, 616716

Whole exome sequencing Gene package Epilepsy version 1, 8‐4‐2015 HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered gene symbol gene ID >10x >20x PEX6 Peroxisome biogenesis disorder 4A (Zellweger), 614862 601498 71 95 91 Peroxisome biogenesis disorder 4B, 614863 Heimler syndrome 2, 616617 PHF6 Borjeson‐Forssman‐Lehmann syndrome, 301900 300414 31 98 73 PHGDH Phosphoglycerate dehydrogenase deficiency, 601815 606879 86 100 99 Neu‐Laxova syndrome 1, 256520 PIGA Paroxysmal nocturnal hemoglobinuria, somatic, 300818 311770 41 93 83 Multiple congenital anomalies‐hypotonia‐seizures syndrome 2, 300868 PIGN Multiple congenital anomalies‐hypotonia‐seizures syndrome 1, 614080 606097 66 98 93 PIGO Hyperphosphatasia with mental retardation syndrome 2, 614749 614730 82 100 100 PLA2G6 Infantile neuroaxonal dystrophy 1, 256600 603604 88 100 99 Neurodegeneration with brain iron accumulation 2B, 610217 Parkinson disease 14, autosomal recessive, 612953 PLCB1 Epileptic encephalopathy, early infantile, 12, 613722 607120 76 100 99 PLP1 Pelizaeus‐Merzbacher disease, 312080 300401 71 100 99 Spastic paraplegia 2, X‐linked, 312920 PNKP Microcephaly, seizures, and developmental delay, 613402 605610 61 100 98 Ataxia‐oculomotor apraxia 4, 616267 PNPO Pyridoxamine 5'‐phosphate oxidase deficiency, 610090 603287 66 100 99 POLG Progressive external ophthalmoplegia, autosomal recessive 1, 258450 174763 86 100 100 Progressive external ophthalmoplegia, autosomal dominant 1, 157640 Mitochondrial DNA depletion syndrome 4B (MNGIE type), 613662 Mitochondrial DNA depletion syndrome 4A (Alpers type), 203700 Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE), 607459 PPT1 Ceroid lipofuscinosis, neuronal, 1, 256730 600722 81 100 100 PQBP1 Renpenning syndrome, 309500 300463 62 100 100 PRICKLE1 Epilepsy, progressive myoclonic 1B, 612437 608500 73 100 97 PRRT2 Episodic kinesigenic dyskinesia 1, 128200 614386 58 100 100 Seizures, benign familial infantile, 2, 605751 Convulsions, familial infantile, with paroxysmal choreoathetosis, 602066 RAB39B Mental retardation, X‐linked 72, 300271 300774 48 100 97 ?Waisman syndrome, 311510 RARS2 Pontocerebellar hypoplasia, type 6, 611523 611524 71 100 95 RNASEH2A Aicardi‐Goutieres syndrome 4, 610333 606034 89 100 100 RNASEH2B Aicardi‐Goutieres syndrome 2, 610181 610326 50 100 88 RNASEH2C Aicardi‐Goutieres syndrome 3, 610329 610330 112 100 100 ROGDI Kohlschutter‐Tonz syndrome, 226750 614574 63 100 98 RPS6KA3 Coffin‐Lowry syndrome, 303600 300075 40 96 81 Mental retardation, X‐linked 19, 300844

Whole exome sequencing Gene package Epilepsy version 1, 8‐4‐2015 HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered gene symbol gene ID >10x >20x RRM2B Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), 612075 604712 87 100 100 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5, 613077 Mitochondrial DNA depletion syndrome 8B (MNGIE type), 612075

SAMHD1 Aicardi‐Goutieres syndrome 5, 612952 606754 76 100 94 ?Chilblain lupus 2, 614415 SCARB2 Epilepsy, progressive myoclonic 4, with or without renal failure, 254900 602257 88 100 100 SCN1A Epilepsy, generalized, with febrile seizures plus, type 2, 604403 182389 100 100 99 Dravet syndrome, 607208 Migraine, familial hemiplegic, 3, 609634 Febrile seizures, familial, 3A, 604403 SCN1B Epilepsy, generalized, with febrile seizures plus, type 1, 604233 600235 102 97 95 Brugada syndrome 5, 612838 Cardiac conduction defect, nonspecific, 612838 Atrial fibrillation, familial, 13, 615377 SCN2A Seizures, benign familial infantile, 3, 607745 182390 100 100 99 Epileptic encephalopathy, early infantile, 11, 613721 SCN8A ?Cognitive impairment with or without cerebellar ataxia, 614306 600702 97 100 99 Epileptic encephalopathy, early infantile, 13, 614558 SCN9A Erythermalgia, primary, 133020 603415 98 100 98 Paroxysmal extreme pain disorder, 167400, Insensitivity to pain, congenital, 243000 Febrile seizures, familial, 3B, 613863 Epilepsy, generalized, with febrile seizures plus, type 7, 613863 Small fiber neuropathy, 133020 {Dravet syndrome, modifier of}, 607208 HSAN2D, autosomal recessive, 243000 SLC16A1 Erythrocyte lactate transporter defect, 245340 600682 76 100 100 Hyperinsulinemic hypoglycemia, familial, 7, 610021 Monocarboxylate transporter 1 deficiency, 616095 SLC19A3 Thiamine metabolism dysfunction syndrome 2 (biotin‐ or thiamine‐responsive encephalopathy type 2), 606152 118 100 100 607483 SLC25A1 Combined D‐2‐ and L‐2‐hydroxyglutaric aciduria, 615182 190315 40 99 90 SLC25A15 Hyperornithinemia‐hyperammonemia‐homocitrullinemia syndrome, 238970 603861 106 90 86 SLC25A22 Epileptic encephalopathy, early infantile, 3, 609304 609302 63 100 100

Whole exome sequencing Gene package Epilepsy version 1, 8‐4‐2015 HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered gene symbol gene ID >10x >20x SLC2A1 GLUT1 deficiency syndrome 1, infantile onset, severe, 606777 138140 104 100 100 GLUT1 deficiency syndrome 2, childhood onset, 612126 {Epilepsy, idiopathic generalized, susceptibility to, 12}, 614847 Dystonia 9, 601042 Stomatin‐deficient cryohydrocytosis with neurologic defects, 608885 SLC35A2 Congenital disorder of glycosylation, type IIm, 300896 314375 29 98 80 SLC6A8 Cerebral creatine deficiency syndrome 1, 300352 300036 19 81 42 SLC9A6 Mental retardation, X‐linked syndromic, Christianson type, 300243 300231 50 100 96 SMS Mental retardation, X‐linked, Snyder‐Robinson type, 309583 300105 39 95 94 SPTAN1 Epileptic encephalopathy, early infantile, 5, 613477 182810 87 100 100 SRPX2 ?Rolandic epilepsy, mental retardation, and speech dyspraxia, 300643 300642 50 99 91 ST3GAL3 Mental retardation, autosomal recessive 12, 611090 606494 111 100 100 Epileptic encephalopathy, early infantile, 15, 615006 STXBP1 Epileptic encephalopathy, early infantile, 4, 612164 602926 92 100 100 SUOX Sulfite oxidase deficiency, 272300 606887 104 100 100 SYN1 Epilepsy, X‐linked, with variable learning disabilities and behavior disorders, 300491 313440 37 86 67 SYNGAP1 Mental retardation, autosomal dominant 5, 612621 603384 55 95 82 SYP Mental retardation, X‐linked 96, 300802 313475 48 100 100 SZT2 Epileptic encephalopathy, early infantile, 18, 615476 615463 57 99 93 TBC1D24 Myoclonic epilepsy, infantile, familial, 605021 613577 92 100 100 Epileptic encephalopathy, early infantile, 16, 615338 DOOR syndrome, 220500 Deafness , autosomal recessive 86, 614617 Deafness, autosomal dominant 65, 616044 TBCE Kenny‐Caffey syndrome, type 1, 244460 604934 80 99 91 Hypoparathyroidism‐retardation‐dysmorphism syndrome, 241410 TCF4 Pitt‐Hopkins syndrome, 610954 602272 73 100 98 Corneal dystrophy, Fuchs endothelial, 3, 613267 TDP2 No OMIM phenotype 605764 73 100 91 TPP1 Ceroid lipofuscinosis, neuronal, 2, 204500 607998 79 100 98 Spinocerebellar ataxia, autosomal recessive 7, 609270 TREX1 Aicardi‐Goutieres syndrome 1, dominant and recessive, 225750 606609 129 100 100 Chilblain lupus, 610448 Vasculopathy, retinal, with cerebral leukodystrophy, 192315 {Systemic lupus erythematosus, susceptibility to}, 152700 TRPM6 Hypomagnesemia 1, intestinal, 602014 607009 81 100 99 UBE3A Angelman syndrome, 105830 601623 61 100 99 ZEB2 Mowat‐Wilson syndrome, 235730 605802 81 100 100

‐ Gene symbols according HGCN

Whole exome sequencing Gene package Epilepsy version 1, 8‐4‐2015 HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered gene symbol gene ID >10x >20x Gene symbols according HGCN ‐ OMIM release used: 17‐3‐2016 ‐ "No OMIM phenotypes" indicates a gene without a current OMIM association ‐ OMIM phenotypes between "[ ]", indicate "nondiseases," mainly genetic variations that lead to apparently abnormal laboratory test values ‐ OMIM phenotypes between "{}", indicate risk factors ‐ OMIM phenotypes with a question mark, "?", before the disease name indicates an unconfirmed or possibly spurious mapping. ‐ The statistics above are based on a set of 50 samples ‐ Median depth is the median of the mean sequence depth over the protein coding exons of the transcript ‐ % Covered 10x describes the percentage of a gene’s coding sequence that is covered at least 10x ‐ % Covered 20x describes the percentage of a gene’s coding sequence that is covered at least 20x

Whole exome sequencing Gene package Epilepsy version 1, 8‐4‐2015